Hyaluronan, also known as hyaluronic acid (HA) or hyaluronate, is a non-sulfated, anionic glycosaminoglycan distributed in various tissues, e.g., connective, epithelial, and neural tissues. HA is a polymer of disaccharides composed of D-glucuronic acid and D-N-acetylglucosamine, which are linked via alternating β1,4- and β1,3-glycosidic bonds. HA has been found to play various physiological roles in the intercellular matrix, including cell migration, proliferation, and differentiation, tissue repair and hydrodynamics, and immune regulation.
Naturally-occurring HA often contains 10,000 or more disaccharide units, the molecular weight of which can reach 4 million daltons or higher. Such high molecular weight HA molecules can be degraded via enzymatic, chemical, or physical methods to produce depolymerized HA products.
High molecular weight HA (e.g., native HA) has anti-angiogenic, anti-inflammatory, and immunosuppressive effects. By contrary, small HA fragments can induce the release of inflammatory chemokine, stimulate CD44 cleavage, increase angiogenesis, and promote tumor cell migration.
In humans, HA is degraded by hyaluronidases, which include six members, e.g., hyaluronidases 1-4 (Hyal 1-Hyal 4) and hyaluronidase PH-20. Among them, Hyal-2 is an anchor protein located on the outer cell membrane via the glycosylphosphatidyl-inositol (GPI) linkage. It was found that HAYL-2 is a receptor of transforming growth factor beta 1 (TGF-β1). Hsu et al., J. Biol. Chem., 284:16049-16059; 2009.